Optimization techniques conformational sampling

Good, A.C. and Cheney, D.L Analysis and optimization of stmcture-based virtual screening protocols (1) exploration of ligand conformational sampling techniques. /. Mol. Graph. Model. 2003, 22, 23-30. 

Finally, it should be pointed out that simple, exact models could be used to test new sampling methodologies [88-90] or optimization techniques [84,91]. A good example is the work by Hao and Scheraga [92], where pairwise contact energy parameters have been optimized to maximize the stability of the native state with respect to other conformations for a 27-mer chain composed of 10 different residues types [92]. 

CD complements fluorescence as a technique for characterizing the folded conformation in solution and for providing, in a single spectrum, a highly specific fingerprint for the native state. It requires only modest amounts of protein and measurements are relatively quick to make. Like fluorescence, its use as a comparative method requires a control spectrum from a carefully characterized sample of the natural or recombinant protein, recorded under defined and optimal conditions, using a spectrometer in good condition. 

Geometry optimization of the proposed mimetic is included as part of the design analysis to ensure the feasibility of the desired molecular conformation. MM and semiempirical quantum mechanical methods have been used most extensively for these purposes. Conformational analysis of the proposed mimetic allows the determination of an energy profile for the molecule under consideration. This has been used by researchers to assess where the desired conformation for the mimetic resides on the molecular potential energy surface. Monte Carlo, MD, and distance geometry-based conformational search techniques have been employed extensively to sample conformational space. Computational methods that attempt to approximate the efifects of aqueous solvation on the conformational profile of the mimetic are being used more frequently as part of these efforts. 

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